This ongoing project evaluates a wide variety of factors which contribute to the urinary excretion of 3-methoxy-r-hydroxyphenylglycol (MHPG), the norepinephrine metabolite thought best to reflect brain turnover. New findings or replications of earlier ones are as follows: (1) Despite an association between the circadian rhythms of MHPG and activity within depressed patients, total 24-hour activity does not correlate with 24-hour MHPG across patients; (2) In a large sample of patients and volunteers, depressed patients with a prior history of mania (bipolar I) have lower MHPG than normals, unipolar depressed or manic patients, although differences are modest; (3) There is a lack of correlation between anxiety and MHPG in our sample of depressed patients, nor is there a correlation between urinary and CSF MHPG; (4) Zimelidine, a serotonergic drug, is able to alter urinary MHPG to the same extent as does desipramine, a noradrenergic agent; (5) The dose response of desipramine-induced urinary MHPG decrease appears to be curvilinear instead of simply linear.